[Cyclic neutropenia. Detection of a mutation in the gene for neutrophil elastase (ELA2)]

Cyclic neutropenia is a rare congenital hematopoietic disease which occurs sporadically or as an autosomal dominantly inherited disorder. Recently, the locus for cyclic neutropenia was mapped to chromosome 19p13.3. Autosomal dominant and sporadic cyclic neutropenia are now attributable to mutations of the ELA2 gene encoding neutrophil elastase.

Based on a case report we review the clinical picture and diagnostic criteria of cyclic neutropenia and report about the recent molecular biological findings and current treatment options.

Serial blood cell counts revealed the characteristic oscillations of the circulating neutrophils with 21-day periodicity from near normal to extremely low levels. The neutrophil nadir lasted 3-5 days. The neutropenia was associated with fever, malaise, painful oral aphthous ulcers and lymphadenopathy. Mutational analysis of the patient's genomic DNA revealed a single base-pair transition (nt 4716, G-->A) in intron 4 of ELA2. Since the initiation of therapy with subcutaneous recombinant human granulocyte-stimulating colony factor (rHuG-CSF) 24 months ago, the patient has been free of symptoms.

Despite the typical medical history with onset of the symptoms in early infancy the diagnosis of cyclic neutropenia was not established until the age of 9 years. A common reason for the delayed diagnosis of cyclic neutropenia may be unawareness of the rare but distinctive disorder and the practice of obtaining screening blood counts without leukocyte differentials. Patients with cyclic neutropenia should be enrolled to the Severe Chronic Neutropenia International Registry (SCNIR).